[Mutagenic activity of 2,4,6-trinitrotoluene: the role of metabolizing enzymes].

Mutagenic activity of 2,4,6-trinitrotoluene (2,4,6-TNT) and one of its derivatives, 2,4-diamino-6-nitrotoluene (2,4-DA-6-NT) was studied in the Ames test using the Salmonella typhimurium tester strains TA98, TA100, TA100NR (deficient in classical nitroreductases), and TA100/1, 8DNP (deficient in O-acetyltransferase). The number of revertants was significantly increased by 2,4,6-TNT, in comparison with that of spontaneous revertants. Base pair substitutions were preferentially induced by 2,4,6-TNT. The mutagenic effect of this compound was virtually altered by in vitro metabolic activation with the S9 fraction of human placenta. Neither 2,4,6-TNT nor 2,4-DA-6-NT exhibited mutagenic activity in the strains TA 100NR and TA 100/1,8DNP. Based on the results obtained, it is concluded that the mutagenic potential of 2,4,6-TNT is determined by its metabolites that form during bacterial metabolism. Bacterial nitroreductases and O-acetyltransferases are the key activators of this compound to form the ultimate mutagens.